The mouse uterus has provided a system for the study of estrogen since it contains estrogen receptors and depends on estrogen stimulation for normal physiological functions. We have previously purified an estrogen-induced secretory protein from mouse uterine luminal fluid. Antibody to this estrogen inducible mouse uterine protein has been used to isolate cDNA to the messenger RNA. Analysis of the deduced primary structure and additional biochemical characterization indicates that the protein is lactotransferrin. We have mapped lactotransferrin gene to human chromosome 3 (q21-q23) and mouse chromosome 9 and shown that it was induced by estrogen in a time and dose-dependent fashion in the uterus but not the mammary gland. A high level of lactotransferrin was detected by immunocytochemistry in uterine epithelial cells 1 day after parturition, but immunoreactivity disappeared quickly thereafter. Lactotransferrin message was, however, relatively abundant in the mammary gland at the end of the lactation period. The presence of lactotransferrin in various tissues also was investigated, and two forms of immunoreactive material were detected. A 70kDa band was found in uterine luminal fluid from the estrogen-stimulated immature mouse and in homogenates of lung, vagina, mammary gland, oviduct, spleen, lymph node, and uterus of the adult female mouse. In addition, a 55kDa band was detected in submaxillary gland, kidney, ovary, and all of the above tissues. Brain and duodenum had no detectable immunoreactive material. In future work, we hope to gain some understanding of the factors leading to lactotransferrin secretion by the uterus and mammary gland in response to different hormonal signals. In addition, we will compare the structure and function of the lactotransferrin gene and the related transferrin gene family.